Opioid agonists, or opioids, are drugs which are used primarily as analgesics. Opioid agonists act on stereospecific receptor sites in the brain, as well as in other parts of the body, which presumably regulate the feeling and perception of pain. Examples of opioid agonists include, but are not limited to, oxycodone, morphine, hydrocodone and codeine. Although they are effective in reducing the perceived pain by a patient, opioid agonists also have the characteristic of possibly being physically and psychologically addictive to the patient if used repeatedly over an extended period of time. Thus, the potential for addiction to or abuse of such drugs is an issue of concern whenever prescribing such drugs as analgesics.
For example, oxycodone is an opioid agonist which has a high potential for abuse. Oxycodone is most often administered orally, and is commercially available in a controlled-released form known as Oxycontin™ (Purdue Pharma). However, the controlled release aspect of an Oxycontin™ dosage form can be bypassed by an abuser by, for example, crushing or grinding up the dosage form, and then eating or snorting the crushed or ground-up Oxycontin™ dosage form. Thus, in this way the abuser is able to receive a relatively large single dose of the oxycodone, resulting in a euphoric “high” being experienced by the abuser.
Opioid antagonists are those drugs which serve to neutralize or block the euphoric or analgesic effect of an opioid agonist. For example, opioid antagonists are often employed to block the euphoric or analgesic effects in individuals who have overdosed on an opioid agonist, or as a daily treatment drug in individuals who are addicted to an opioid agonist. It is thought that the opioid antagonists act on and compete for the same stereospecific receptor sites in the brain as the opioid agonists, and thereby neutralize or block the resulting-analgesic or euphoric effects of the opioid agonist.
Thus, there have been previous attempts in the prior art to produce formulations and methods concerned with reducing the abuse potential of opioid agonists. For example, U.S. Pat. No. 6,228,863 to Palermo et al. describes a method of preventing the abuse of opioid dosage forms by combining an orally active opioid agonist with an opioid antagonist into an oral dosage form which would require at least a two-step extraction process to separate the opioid antagonist from the opioid agonist. According to Palermo et al., the oral dosage forms described therein had less parenteral and/or oral abuse potential than that of the prior art oral dosage forms.
In addition, U.S. Pat. No. 6,277,384 to Kaiko et al. describes oral dosage forms including combinations of opioid agonists and opioid antagonists in ratios which are analgesically effective when administered orally, but which are aversive in a physically dependent individual. According to Kaiko et al., the oral dosage forms described therein had less oral abuse potential than that of the prior art oral dosage forms.
Furthermore, U.S. Pat. No. 5,236,714 to Lee et al. is directed to an abusable substance dosage form having a reduced abuse potential. Lee et al. disclose compositions and dosage forms for administering abusable substances wherein the therapeutic effect of the abusable substance will not be diminished, although the abuse potential of the abusable substance will be diminished. Specifically, topical compositions for application to a patient's skin or mucosa are disclosed including an abusable substance present in a form which is permeable to the skin or mucosa to which the composition is to be applied, and an antagonist present in a form which is impermeable to the skin or mucosa to which the composition is to be applied, such that if an attempt were made to abuse the composition by administering it through another bodily portal, the antagonist would prevent the occurrence of the abusive effect by producing its antagonistic effect. In addition, Lee et al. disclose dosage forms comprising a drug reservoir composition including an abusable substance and at least one antagonist enclosed within an abusable substance releasing means, wherein the abusable substance is present in a form which is permeable through the releasing means and the antagonist is present in a form which is impermeable to the releasing means. As with the topical composition, Lee et al. disclose that if an attempt were made to abuse the drug reservoir composition by removing it from the dosage form and administering it through another bodily portal, the antagonist would prevent the occurrence of the abusive effect by producing its antagonistic effect. The dosage forms of Lee et al. include a single abusable substance releasing means which controls the release of both the abusable substance and the antagonist.
However, there is still a need in the art for an improved oral dosage form of an opioid antagonist which would reduce the abuse potential of an opioid agonist.